Inflammation and activation of immune cells are key mechanisms in the development of atherosclerosis. Previous data indicate important roles for monocytes and T-lymphocytes in lesions. However, recent data suggest that neutrophils also may be of importance in atherogenesis. Here, we use apolipoprotein E (ApoE)-deficient mice with fluorescent neutrophils and monocytes (ApoE ؊/؊ /Lys EGFP/EGFP mice) to specifically study neutrophil presence and recruitment in atherosclerotic lesions. We show by flow cytometry and confocal microscopy that neutrophils make up for 1.8% of CD45 ؉ leukocytes in the aortic wall of ApoE ؊/؊ /Lys EGFP/EGFP mice and that their contribution relative to monocyte/macrophages within lesions is approximately 1:3. However, neutrophils accumulate at sites of monocyte high density, preferentially in shoulder regions of lesions, and may even outnumber monocyte/macrophages in these areas. Furthermore, intravital microscopy established that a majority of leukocytes interacting with endothelium on lesion shoulders are neutrophils, suggesting a significant recruitment of these cells to plaque. These data demonstrate neutrophilic granulocytes as a major cellular component of atherosclerotic lesions in ApoE ؊/؊ mice and call for further study on the roles of these cells in atherogenesis. Recruitment of immune cells to the arterial intima is central to atherogenesis. Current dogma emphasizes the role of macrophages and T-lymphocytes in promoting plaque development and destabilization.1,2 However, the most abundant white blood cell in the circulation, the neutrophilic granulocyte, has until recently rarely been associated with the development of atherosclerosis. Nonetheless, proteins typically secreted by neutrophils are abundant in lesions, [3][4][5][6][7] and systemic neutrophil counts appear to correlate closely with severity of atherosclerosis in humans.8 Similar observations were also recently made in the murine system in which increased peripheral neutrophil count was associated with enhanced plaque size, whereas the opposite was true when neutrophils were depleted from the circulation. There are also data that indicate presence of neutrophils in lesions of low-density lipoprotein (LDL) receptor-deficient mice.5 Despite these findings, data on potential roles of neutrophils in atherogenesis are rare in the literature.We recently crossed apolipoprotein E-deficient ApoE mice, which allow for sensitive detection of neutrophils in atherosclerotic plaques. 11 Here, we study the presence and spatial distribution of neutrophils in atherosclerotic arteries of these mice. We demonstrate that neutrophils are present in substantial numbers in aortic plaque. Moreover, their contribution is higher in shoulder regions of plaque, which are areas of high inflammatory activity. Intravital microscopy further revealed that neutrophils are the main cell population that interacts with atherosclerotic endothelium, suggesting an ongoing recruitment of neutrophils to lesions. These data demonstrate that neutrophils represen...

This cohort study compares the risks of venous thromboembolism (VTE) recurrence in patients receiving non–vitamin K antagonist oral anticoagulants (NOACs) vs low-molecular-weight heparin in Asian individuals with cancer.

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